A model for the intrinsic limit of cancer therapy: Duality of treatment-induced cell death and treatment-induced stemness.

Intratumor cellular heterogeneity and non-genetic cell plasticity in tumors pose a recently recognized challenge to cancer treatment. Because of the dispersion of initial cell states within a clonal tumor cell population, a perturbation imparted by a cytocidal drug only kills a fraction of cells. Due to dynamic instability of cellular states the cells not killed are pushed by the treatment into a variety of functional states, including a "stem-like state" that confers resistance to treatment and regenerative capacity. This immanent stress-induced stemness competes against cell death in response to the same perturbation and may explain the near-inevitable recurrence after any treatment. This double-edged-sword mechanism of treatment complements the selection of preexisting resistant cells in explaining post-treatment progression. Unlike selection, the induction of a resistant state has not been systematically analyzed as an immanent cause of relapse. Here, we present a generic elementary model and analytical examination of this intrinsic limitation to therapy. We show how the relative proclivity towards cell death versus transition into a stem-like state, as a function of drug dose, establishes either a window of opportunity for containing tumors or the inevitability of progression following therapy. The model considers measurable cell behaviors independent of specific molecular pathways and provides a new theoretical framework for optimizing therapy dosing and scheduling as cancer treatment paradigms move from "maximal tolerated dose," which may promote therapy induced-stemness, to repeated "minimally effective doses" (as in adaptive therapies), which contain the tumor and avoid therapy-induced progression.

Statistical Analysis of Random Motion and Energetic Behavior of Counting: Gibbs' Theory Revisited.

Following a recently reformulated Gibbs' statistical chemical thermodynamic theory on discrete state space, we present a treatment on statistical measurements of random mechanical motions in continuous space. In particular, we show how the concept of temperature and an ideal gas/solution law arise from a statistical analysis of a collection of independent and identically distributed complex particles without relying on Newtonian mechanics, nor the very concept of mechanical energy. When sampling from an ergodic system, the data ad infinitum limit elucidates how the entropy function characterizes randomness among measurements with the emergence of a novel energetic representation for the statistics and an internal energy additivity. This generalization of Gibbs' theory is applicable to statistical measurements on single living cells and other complex biological organisms, one individual at a time.

Demand for medication abortion among public university students in Washington.

Provision of medication abortion in student health centers is safe and effective, but no public universities in Washington state provide such services. We estimate demand for medication abortion and describe barriers to care among students at four-year public universities in Washington. Using publicly available data, we estimated that students at the 11 Washington public universities obtained between 549 and 932 medication abortions annually. Students must travel an average of 16 miles (range:1-78) or 73 minutes via public transit (range:22-284) round trip to the nearest abortion-providing facility. Average wait time for the first available appointment was 10 days (range:4-14), and average cost was $711. Public universities can play an integral role in expanding abortion access post-Dobbs by providing medication abortion, effectively reducing barriers to care for students. The state legislature can pass legislation requiring universities to provide medication abortion, similar to what other states also protective of abortion rights have done.